An Analysis of Major Causes of Surgical Failure Using Bähren System in Intraoperative Venography During Varicocelectomy

Purpose: In young patients with varicocele, preservation of the internal spermatic artery may be advantageous for catch-up growth, but it may also increase the likelihood of treatment failure. Intraoperative venography reduces the likelihood that unsealed veins will remain after varicocelectomy. We analyzed the characteristics of remnant veins visualized through intraoperative venography to investigate the cause of surgical failure in artery-sparing varicocelectomy (ASV). Materials and methods: We retrospectively analyzed clinical characteristics and outcomes of patients aged 18 years or younger who underwent varicocelectomy with intraoperative venography from January 2005 to December 2017. During varicocelectomy, intraoperative venography was performed to distinguish veins from other structures. Any unsealed veins that were discovered were ligated and classified using the Bahren system. Results: One hundred and sixty-two patients underwent intraoperative venography: 153 cases (94.4%) were for primary varicocelectomy, and 9 cases (5.6%) were for repeat varicocelectomy. Open varicocelectomy was performed in 105 cases (64.8%), and laparoscopic varicocelectomy was performed in 57 cases (35.2%). Venography revealed remnant veins after the first ligation in 51 cases (31.2%), 46 (90.2%) and 5 (9.8%) of which were Bähren types 3 and 4, respectively. Five patients (3.1%) experienced varicocele recurrence, classified as persistence in 1 patient (0.6%) and relapse in 4 patients (2.5%). Conclusion: Remnant collateral veins of the internal spermatic vein (ISV) (Bahren type 3) are the most common cause of failure in ASV. In a few patients, an external spermatic vein merges with the ISV at a higher level (Bahren type 4) and is unidentifiable without venography.ope

Dose-Ranging Study of Ramosetron for the Prevention of Nausea and Vomiting after Laparoscopic Gynecological Surgery: A Prospective Randomized Study

Patients undergoing laparoscopic gynecologic surgery and receiving postoperative analgesia with opioids have a high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of three doses of ramosetron in this high-risk population. In this prospective, double-blind trial, 174 patients randomly received ramosetron 0.3 mg (R0.3 group; n = 58), 0.45 mg (R0.45 group; n = 58), or 0.6 mg (R0.6 group; n = 58) at the end of surgery. The primary outcome was the incidence of PONV during the first postoperative 48 h. Nausea severity, pain scores, adverse events, and patient satisfaction (1-4; 4, excellent) were assessed. The incidence of PONV was not different between groups (35%, 38%, and 35% in R0.3, R0.45, and R0.6 groups; p = 0.905). Nausea severity, pain scores, and incidence of adverse events (dizziness, headache, or sedation) were similar between groups. Compared to the R0.3 group, the R0.45 and R0.6 groups had lower incidence of premature discontinuation of fentanyl-based patient-controlled analgesia primarily because of intractable PONV (9% and 5% vs. 24%; p = 0.038), and higher satisfaction scores (3.4 ± 0.8 and 3.3 ± 0.7 vs. 2.4 ± 0.9; p = 0.005). Compared to ramosetron 0.3 mg, ramosetron 0.45 and 0.6 mg did not reduce PONV, but reduced premature discontinuation of patient-controlled analgesia and increased patient satisfaction, without increasing adverse events.ope

A Pilot Study Testing the Efficacy of dCBT in Patients With Cancer Experiencing Sleep Problems

Objective: This pilot study aimed to evaluate the efficacy of a digital cognitive behavioral therapy (dCBT) in patients with cancer experiencing sleep problems. Methods: A total of 57 participants aged 25-65 years (6M/51F with a mean of 42.80 years and a standard deviation of 14.15 years) were randomly assigned to three groups-21 participants to a dCBT program (HARUToday Sleep), 20 participants to an app-based attentional control program (HARUCard Sleep), and 16 participants to a waitlist control group-and evaluated offline before and after the program completion. Of the 57 participants, there were a total of 45 study completers, 15 participants in each group. The dependent variables were sleep quality scores, measured by the Pittsburgh Sleep Quality Index (PSQI) and health-related quality of life scores, measured using the Short-Form 36 (SF-36), and attentional bias scores from a dot-probe computer task. Results: For both the intention-to-treat (N = 57) and study-completers analyses (N = 45, 15 for each group), a significant increase supported by a large effect size was found in the quality of sleep score of the HARUToday Sleep group compared to both the app-based attentional control and the waitlist control group. However, no significant changes were found in the quality of life and attentional bias scores. Conclusion: Our results suggest that the HARUToday Sleep app has the potential to serve as an intervention module to enhance the sleep quality of patients with cancer experiencing sleep problems.ope

Preliminary Results From a Randomized Controlled Study for an App-Based Cognitive Behavioral Therapy Program for Depression and Anxiety in Cancer Patients

Cancer patients experience various psychological and social difficulties, the most common being depression and anxiety. The purpose of this study was to develop and evaluate the effectiveness of an app-based cognitive behavioral therapy program for depression and anxiety in cancer patients. For this purpose, 63 participants who met the inclusion criteria were randomly assigned to either a mobile-application-based cognitive behavioral therapy program (HARUToday), a simple information-provision mobile-application-based program (HARUCard), or a waitlist control group. Self-report questionnaires including the Beck Depression Inventory, State-Trait Anxiety Inventory, Health-Related Quality of Life Scale, Dysfunctional Attitude Scale, and two computer tasks including the dot-probe task and the Implicit Association Test, were administered before and after 66 days of intervention. The results showed that the Beck Depression Inventory and State-Trait Anxiety Inventory scores of the cognitive behavioral therapy program (HARUToday) group decreased significantly after the intervention compared to the attention control (HARUCard) and waitlist control groups. However, there were no significant changes in scores of the Health-Related Quality of Life Scale and Dysfunctional Attitude Scale, and the two computer tasks. Such results suggest that a mobile-application-based cognitive behavioral therapy program may be an effective intervention for alleviating depression and anxiety, but not the general quality of life of cancer patients. Taking into consideration that psychosocial problems may not the topmost priority for cancer patients who are facing a chronic and possibly mortal disease, a mobile-application cognitive behavioral therapy program may be a possible solution for the alleviation of depression and anxiety in cancer patients who have many restraints in terms of time and space.ope

Relationship between the expression of cyclin B1, D1 and the various prognostic factors in ovarian carcinoma

Objective: The objective of this study was to evaluate the relationship between the expression of cyclin B1, D1 and the various prognostic factors in ovarian carcinoma. Methods: In this study, fresh ovarian tissue samples were obtained from 41 patients treated surgically at our institute from March of 2002 to February of 2005. These included 36 ovarian carcinomas and 5 normal ovarian tissues that were served as the control. Quantitative real-time RT-PCR and Western blot analysis were used in detecting the expression of mRNA and protein of cyclin B1, D1, respectively. Results: The mean 2(-delta delta CT) values of cyclin B1 and D1 mRNA in ovarian carcinoma tissues obtained through quantitative real-time RT-PCR were 5.83+/-12.03, 17.60+/-22.20, respectively, and the mean values in the control were 0.55+/-0.35, 0.50+/-0.26, respectively. The results showed difference in the expression, but were not statistically significant (p=0.67, 0.07, respectively). If the mean densitometer value of cyclin B1 and D1 protein in the control obtained by Western blot analysis was 1, the mean values in ovarian carcinoma tissues were higher, but were not statistically significant (1.30+/-0.73, 1.81+/-1.28, respectively) (p=0.76, 0.06, respectively). The expression of cyclin B1, D1 and various prognostic factors was not statistically related. Conclusion: Our results showed that the expression of cyclin B1 and D1 in ovarian carcinoma tissues was higher than in the normal control. This suggested that cyclin B1, D1 and the tumorigenesis and the degree of malignancy was closely related. But the expression of cyclin B1, D1 and various prognostic factors was not statistically related. Further studies based on the correlation between cyclin and response to treatment or survival rate are needed to support cyclin as a prognostic factor of ovarian carcinoma.ope

Correlation of HLA-G Gene Expression with Various Prognostic Factors in the Tissue of Ovarian Carcinoma

Objective: The objective of this study was to investigate the relationship between the expression of mRNA and protein of HLA-G and other clinicopathologic prognostic factors of ovarian cancer. Methods: 43 patients diagnosed with ovarian cancer from 1997 to 2005 and 5 patients with normal ovarian tissue (controls) were enrolled in this prospective study. The patient group all went through baseline studies with staging laparotomy and adjuvant chemotherapy. Quantitative real-time RT PCR and Western blot analysis were used in detecting the expression of mRNA and protein of HLA-G. Results: The mRNA expression of HLA-G (2-delta delta Ct value) in cancer group were 1.21 (0-9), and 0.01 (0-0.02) in control group, which was statistically significant (P=0.005). The expressed protein levels did not show any difference between the cancer and control groups. There also was a significant relationship between the serum CA 125 at the time of diagnosis and the HLA-G protein levels (P=0.02). But the relationship between other clinicopathologic prognostic factors and the HLA-G protein levels were not statistically significant. Conclusion: Our results showed that HLA-G mRNA expression level was much higher in ovarian cancer patient group than in those of control group. Therefore HLA-G maybe play an important role in carcinogenesis of ovarian cancer. Although the protein level of HLA-G had low significance with other prognostic factors, serum CA 125 showed a statistically significant relation with protein levels of HLA-G. Further studies based on the correlation between HLA-G and survival rate are needed to support HLA-G as a prognostic factor of ovarian cancer.ope

Response to letter to editor: indocyanine green fluorescent image-guided inguinal sentinel node biopsy for vulvar cancer: criteria and intraoperative challenges

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A screen for inducers of bHLH activity identifies pitavastatin as a regulator of p21, Rb phosphorylation and E2F target gene expression in pancreatic cancer

The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity. A screen of 4,375 known drugs identified 70 bHLH activators. Prominent among the hits were members of the statin class of HMG-CoA reductase inhibitors, cholesterol lowering drugs that are also being evaluated in cancer. Studies with pitavastatin in primary patient derived tumor cells and established PDA lines, revealed dose dependent growth inhibition. At the molecular level, pitavastatin induced expression of the cyclin dependent kinase (CDK) inhibitor p21 in a cholesterol independent manner, blocked repressive phosphorylation of the Retinoblastoma tumor suppressor protein at CDK targeted sites, and reduced expression of E2F target genes required for progression through the G1/S boundary. Together, the data provide new insight into mechanisms by which statins constrain proliferation in cancer and establish the effectiveness of a novel screening platform to identify small molecules of clinical relevance in pancreatic cancer.ope

Rapid Detection of Duplication/Deletion of the PMP22 Gene in Patients with Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy with Liability to Pressure Palsy by Real-time Quantitative PCR using SYBR Green I Dye

Mutations and altered gene dosage of the peripheral myelin protein (PMP22) gene in chromosome 17p11.2-12 are the main causes for hereditary neuropathies, accounting for approximately 70% of all cases. Patients with duplication of the PMP22 develop Charcot-Marie-Tooth disease type 1A (CMT1A) and deletion of one PMP22 allele leads to hereditary neuropathy with liability to pressure palsy (HNPP). Twenty patients with CMT1A, 17 patients with HNPP, and 18 normal family members and 28 normal controls were studied by real-time quantitative PCR using SYBR Green I on the ABI 7700 Sequence Detection System. The copy number of the PMP22 gene was determined by the comparative threshold cycle method and the albumin was used as a reference gene. The PMP22 duplication ratio ranged from 1.45 to 2.06 and the PMP22 deletion ratio ranged from 0.42 to 0.64. The PMP22 ratio in normal controls, including normal family members, ranged from 0.85 to 1.26. No overlap was found between patients with CMT1A or patients with HNPP and normal controls. This method is fast, highly sensitive, specific, and reproducible in detecting PMP22 duplication and deletion in CMT1A and HNPP patients, respectively.ope

The basic helix-loop-helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) initiates from quiescent acinar cells that attain a Kras mutation, lose signaling from basic helix-loop-helix (bHLH) transcription factors, undergo acinar-ductal metaplasia, and rapidly acquire increased growth potential. We queried whether PDA cells can be reprogrammed to revert to their original quiescent acinar cell state by shifting key transcription programs. METHODS: Human PDA cell lines were engineered to express an inducible form of the bHLH protein E47. Gene expression, growth, and functional studies were investigated using microarray, quantitative polymerase chain reaction, immunoblots, immunohistochemistry, small interfering RNA, chromatin immunoprecipitation analyses, and cell transplantation into mice. RESULTS: In human PDA cells, E47 activity triggers stable G0/G1 arrest, which requires the cyclin-dependent kinase inhibitor p21 and the stress response protein TP53INP1. Concurrently, E47 induces high level expression of acinar digestive enzymes and feed forward activation of the acinar maturation network regulated by the bHLH factor MIST1. Moreover, induction of E47 in human PDA cells in vitro is sufficient to inhibit tumorigenesis. CONCLUSIONS: Human PDA cells retain a high degree of plasticity, which can be exploited to induce a quiescent acinar cell state with reduced tumorigenic potential. Moreover, bHLH activity is a critical node coordinately regulating human PDA cell growth versus cell fate.ope